O-methylasparvenone, a nitrogen-free serotonin antagonist.
O-Methylasparvenone (1) and asparvenone (2) were isolated from an Aspergillus parvulus Smith broth in a microbial screening for 5-HT2C ligands and found to be 5-HT2C antagonists. They represent the first nitrogen-free serotonin ligands. The absolute configuration of 1 was determined to be S by X-ray analysis of the corresponding Mosher-ester. A short and efficient synthesis of rac-1 was developed. This protocol was applied to the synthesis of derivatives of 1 and a structure-affinity relationship was established.
Bös
M
M
Pharma Division, Preclinical CNS Research, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Canesso
R
R
Inoue-Ohga
N
N
Nakano
A
A
Takehana
Y
Y
Sleight
A J
AJ
D016475:3T3 Cells; D000818:Animals; D001230:Aspergillus; D051379:Mice; D008958:Models, Molecular; D009284:Naphthols / Q000302:isolation & purification* / Q000494:pharmacology; D011869:Radioligand Assay; D011985:Receptors, Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000302:isolation & purification* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D009284:Naphthols; C111197:O-methylasparvenone; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C010292:asparvenone